tbuckley/cabot-search huggingface dataset:
Refractory hepatic hydrothorax is associated with increased mortality with death occurring at lower MELD-Na compared to cirrhosis and refractory ascites
Authors: Allison Chin, Dustin R. Bastaich, Bassam Dahman, David E. Kaplan, Tamar H. Taddei, Binu V. John
Journal: Hepatology (2023)

Background and Aims: Although refractory hepatic hydrothorax (RH) is a serious complication of cirrhosis, waitlisted patients do not receive standardized Model for End-stage Liver Disease (MELD) exemption because of inadequate evidence suggesting mortality above biochemical MELD. This study aimed to examine liver-related death (LRD) associated with RH compared to refractory ascites (RA). Approach and Results: This was a retrospective cohort study of Veterans with cirrhosis. Eligibility criteria included participants with RH or RA, followed from their first therapeutic thoracentesis/second paracentesis until death or transplantation. The primary outcome was LRD with non-LRD or transplantation as competing risk. Of 2552 patients with cirrhosis who underwent therapeutic thoracentesis/paracentesis, 177 met criteria for RH and 422 for RA. RH was associated with a significantly higher risk of LRD (adjusted HR [aHR] 4.63, 95% CI 3.31–6.48) than RA overall and within all MELD-sodium (MELD-Na) strata (&lt;10 aHR 4.08, 95% CI 2.30–7.24, 10–14.9 aHR 5.68, 95% CI 2.63–12.28, 15–24.9 aHR 4.14, 95% CI 2.34–7.34, ≥25 aHR 7.75, 95% CI 2.99–20.12). LRD was higher among participants requiring 1 (aHR 3.54, 95% CI 2.29–5.48), 2–3 (aHR 4.39, 95% CI 2.91–6.63), and ≥4 (aHR 7.89, 95% CI 4.82–12.93) thoracenteses relative to RA. Although participants with RH and RA had similar baseline MELD-Na, LRD occurred in RH versus RA at a lower MELD-Na (16.5 vs. 21.82, p =0.002) but higher MELD 3.0 (27.85 vs. 22.48, p &lt;0.0001). Conclusions: RH was associated with higher risk of LRD than RA at equivalent MELD-Na. By contrast, MELD 3.0 may better predict risk of LRD in RH.
Impact of PNPLA3 I148M on alpha-1 antitrypsin deficiency-dependent liver disease progression
Authors: Ines Volkert, Malin Fromme, Carolin Schneider, Lena Candels, Cecilia Lindhauer, Huan Su, Katrine Thorhauge, Monica Pons, Mohamed Ramadan Mohamed, Kai Markus Schneider, Pavel Strnad, Christian Trautwein
Journal: Hepatology (2023)

Background and Aims: Genetic risk factors are major determinants of chronic liver disease (CLD) progression. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M polymorphism and alpha-1 antitrypsin (AAT) E342K variant, termed PiZ, are major modifiers of metabolic CLD. Both variants are known to affect metabolic CLD through increased endoplasmic reticulum stress, but their combined effect on CLD progression remains largely unknown. Here, we aimed to test our working hypothesis that their combined incidence triggers CLD disease progression. Approach and Results: We showed that patients with PiZZ/PNPLA3 I148M from the European alpha-1-antitrypsin deficiency (AATD) liver consortium and the UK Biobank had a trend towards higher liver enzymes, but no increased liver fat accumulation was evident between subgroups. After generating transgenic mice that overexpress the PiZ variant and simultaneously harbor the PNPLA3 I148M knockin (designated as PiZ/PNPLA3 I148M ), we observed that animals with PiZ and PiZ/PNPLA3 I148M showed increased liver enzymes compared to controls during aging. However, no significant difference between PiZ and PiZ/PNPLA3 I148M groups was observed, with no increased liver fat accumulation over time. To further study the impact on CLD progression, a Western-styled diet was administered, which resulted in increased fat accumulation and fibrosis in PiZ and PiZ/PNPLA3 I148M livers compared to controls, but the additional presence of PNPLA3 I148M had no impact on liver phenotype. Notably, the PiZ variant protected PNPLA3 I148M mice from liver damage and obesity after Western-styled diet feeding. Conclusion: Our results demonstrate that the PNPLA3 polymorphism in the absence of additional metabolic risk factors is insufficient to drive the development of advanced liver disease in severe AATD.
Effects on Cancer Prevention from the COVID-19 Pandemic
Authors: Stephen W. Duffy, Lucie de Jonge, Thomas E. Duffy
Journal: Annual Review of Medicine (2023)

The COVID-19 pandemic led to disruption of health services around the world, including cancer services. We carried out a narrative review of the effect of the pandemic on cancer prevention services, including screening. Services were severely affected in the early months of the pandemic, and in some areas are still recovering. Large numbers of additional cancers or additional late-stage cancers have been predicted to arise over the coming years as a result of this disruption. To minimize the effects on cancer outcomes, it is necessary to return as quickly as possible to prepandemic levels of screening and prevention activity or indeed to exceed these levels. The recovery of services should address health inequalities. Expected final online publication date for the Annual Review of Medicine, Volume 75 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Uniting to defeat steatotic liver disease: A global mission to promote healthy livers and healthy lives
Authors: Aleksander Krag, Maria Buti, Jeffrey V. Lazarus, Alina M. Allen, Jacqueline Bowman, Patrizia Burra, Giacomo Donnini, Ajay Duseja, Manal H. El-Sayed, Amalia Gastaldelli, Ben Hainsworth, Tom H. Karlsen, Michael Kessler, Marko Korenjak, Henry E. Mark, Jake P. Mann, Veronica Miller, Mário G. Pessoa, Daniel Piñeiro, Shiv K. Sarin, Shivaram P. Singh, Mary E. Rinella, José Willemse, Zobair M. Younossi, Sven M. Francque
Journal: Journal of Hepatology (2023)
Social Media Interventions for Patients and Public: Opportunities and Challenges for the Urology Community
Authors: Nikita R. Bhatt, Jeremy Yuen-Chun Teoh, Esther Garcia Rojo, Vineet Gauhar, Claudia Mercader, Vito Cucchiara, Carla Bezuidenhout, Eamonn Rogers, Maria J. Ribal, Gianluca Giannarini
Journal: European Urology (2023)
Identifying <i>STRN3-RARA</i> as a new fusion gene for acute promyelocytic leukemia
Authors: Qi Zhang, He Li, Xuelan Chen, Fan Gu, Lanxin Zhang, Lu Zhang, Tong Chen, Qiang Chen, Wentong Meng, Yu Wu, Hong Chang, Ting Liu, Chong Chen, Hongbing Ma, Yu Liu
Journal: Blood (2023)
Essential emergency skincare: a global health dermatology innovation for Myanmar and beyond
Authors: Kyaw Zin Htet, Christopher E M Griffiths, Su M Lwin
Journal: British Journal of Dermatology (2023)

Myanmar provides an exemplar framework whereby a global health dermatology partnership, developed during a time of political stability, has led to an innovative emergency essential skincare strategy to sustain its overarching mission of providing quality care for people with skin disease at times of conflict and instability. This framework, through multilevel integrated approaches such as education and service delivery, serves as a model for crisis-responsive healthcare and global health goals.
The Gene Expression Classifier ALLCatchR Identifies B-cell Precursor ALL Subtypes and Underlying Developmental Trajectories Across Age
Authors: Thomas Beder, Björn-Thore Hansen, Alina M. Hartmann, Johannes Zimmermann, Eric Amelunxen, Nadine Wolgast, Wencke Walter, Marketa Zaliova, Željko Antić, Philippe Chouvarine, Lorenz Bartsch, Malwine J. Barz, Miriam Bultmann, Johanna Horns, Sonja Bendig, Jan Kässens, Christoph Kaleta, Gunnar Cario, Martin Schrappe, Martin Neumann, Nicola Gökbuget, Anke Katharina Bergmann, Jan Trka, Claudia Haferlach, Monika Brüggemann, Claudia D. Baldus, Lorenz Bastian
Journal: HemaSphere (2023)

Current classifications (World Health Organization-HAEM5/ICC) define up to 26 molecular B-cell precursor acute lymphoblastic leukemia (BCP-ALL) disease subtypes by genomic driver aberrations and corresponding gene expression signatures. Identification of driver aberrations by transcriptome sequencing (RNA-Seq) is well established, while systematic approaches for gene expression analysis are less advanced. Therefore, we developed ALLCatchR, a machine learning-based classifier using RNA-Seq gene expression data to allocate BCP-ALL samples to all 21 gene expression-defined molecular subtypes. Trained on n = 1869 transcriptome profiles with established subtype definitions (4 cohorts; 55% pediatric / 45% adult), ALLCatchR allowed subtype allocation in 3 independent hold-out cohorts (n = 1018; 75% pediatric / 25% adult) with 95.7% accuracy (averaged sensitivity across subtypes: 91.1% / specificity: 99.8%). High-confidence predictions were achieved in 83.7% of samples with 98.9% accuracy. Only 1.2% of samples remained unclassified. ALLCatchR outperformed existing tools and identified novel driver candidates in previously unassigned samples. Additional modules provided predictions of samples blast counts, patient’s sex, and immunophenotype, allowing the imputation in cases where these information are missing. We established a novel RNA-Seq reference of human B-lymphopoiesis using 7 FACS-sorted progenitor stages from healthy bone marrow donors. Implementation in ALLCatchR enabled projection of BCP-ALL samples to this trajectory. This identified shared proximity patterns of BCP-ALL subtypes to normal lymphopoiesis stages, extending immunophenotypic classifications with a novel framework for developmental comparisons of BCP-ALL. ALLCatchR enables RNA-Seq routine application for BCP-ALL diagnostics with systematic gene expression analysis for accurate subtype allocation and novel insights into underlying developmental trajectories.
Discussions About Goals of Care and Advance Care Planning Among Adolescents and Young Adults With Cancer Approaching the End of Life
Authors: Jennifer W. Mack, Colin Cernik, Hajime Uno, Lanfang Xu, Cecile A. Laurent, Lauren Fisher, Nancy Cannizzaro, Julie Munneke, Robert M. Cooper, Joshua R. Lakin, Corey M. Schwartz, Mallory Casperson, Andrea Altschuler, Lori Wiener, Lawrence Kushi, Chun R. Chao
Journal: Journal of Clinical Oncology (2023)

Adolescents and young adults (AYAs) with cancer receive high rates of medically intensive measures at the end of life. This study aimed to characterize the prevalence and timing of conversations about goals of care and advance care planning among AYAs at the end of life as one potential influence on care received.
In This Issue of <i>Diabetes Care</i>
Authors: Max Bingham
Journal: Diabetes Care (2023)

The complex relationship between neighborhood environments and diabetes risk and outcomes is explored by Mujahid et al. (p.1609).They set out a framework that links the two across a continuum of risks and social/physical factors that very much reflect the historical and current social issues faced by many in the U.S. Starting from the perspective that behavioral and biological factors alone do not fully explain widespread inequities in diabetes risk, they look at various aspects of the built environment that might also affect the risk for diabetes.Specifically, they look at the physical built environment as well as factors that might arise because of the way it was built.These include area poverty and deprivation, access to food and recreational spaces, aesthetics, air pollution, social cohesion, disorder, safety, and crime, among others.In all cases, the authors provide example studies that link the built environment and subsequent risk for diabetes, although evident issues remain with methodologies and translating findings to real-world changes.A major theme to also emerge is the outsized influence of historic and structural racism on current general disease risks and specifically diabetes risk.They highlight numerous studies that show how historic practices (slavery, racism, segregation, and even terrorism) have influenced the design of neighborhood environments and how in myriad ways they have created inequities in health risks, including those for diabetes.The authors go on to make a series of recommendations for future research and the observational and interventional studies that might be needed to address many of the issues they identify.They also look at the research needed to address health inequities that the built environment influences, particularly to address structural racism that still appears rampant in the U.S. Interestingly, they also show how neighborhood-level factors might be incorporated into clinical care to identify local communities with high medical and social needs to develop interventions that improve diabetes outcomes.
Skin is a window to one’s inner world
Authors: Viktoria Eleftheriadou, Andrew R Thompson
Journal: British Journal of Dermatology (2023)

e p t e d fo r p u blic a tio n.Cit a tio n fo r fin al p u blis h e d ve r sio n: El eft h e ri a d o u, Vikto ri a a n d Tho m p s o n, An d r e w 2 0 2 3. S ki n is a wi n d o w t o o n e ' s in n e r w o rl d.B ritis h Jou r n al of D e r m a t olo gy 1 8 9 (5) , p p. 5 0 1-5 0 2. 1 0.
The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor
Authors: Livia Stanger, Adriana Yamaguchi, Pooja Yalavarthi, Sylviane Lambert, Devin Gilmore, Andrew Rickenberg, Catherine Luke, Kiran Kumar, Andrea T. Obi, Andrew White, Niklas Bergh, Björn Dahlöf, Michael Holinstat
Journal: Blood (2023)
Early B-cell development and B-cell maturation are impaired in patients with active hemophagocytic lymphohistiocytosis
Authors: Jenny Shim, Sunita Park, Suresh Venkateswaran, Deepak Kumar, Chengyu Prince, Vaunita Parihar, Larkin Maples, Edmund K. Waller, Subra Kugathasan, Michael Briones, Miyoung Lee, Curtis J. Henry, Sampath Prahalad, Shanmuganathan Chandrakasan
Journal: Blood (2023)
Effect of a Community Health Worker–Led Intervention Among Low-Income and Minoritized Patients With Cancer: A Randomized Clinical Trial
Authors: Manali I. Patel, Kris Kapphahn, Emily Wood, Tumaini Coker, Deborah Salava, Angela Riley, Ivana Krajcinovic
Journal: Journal of Clinical Oncology (2023)

PURPOSE To determine whether a community health worker (CHW)–led intervention could improve health-related quality of life (HRQoL; primary outcome) more than usual care among low-income and racial and ethnic minoritized populations newly diagnosed with cancer. METHODS This randomized clinical trial was conducted from November 1, 2018, until August 31, 2021, in outpatient cancer clinics in Atlantic City, NJ, and Chicago, IL. Hourly low-wage worker members of an employer union health fund age 18 years or older with newly diagnosed solid tumor and hematologic malignancies were randomly assigned 1:1 to usual care (control group) or usual care augmented with a trained CHW for 12 months (intervention group). The CHW assisted participants with advance care planning (ACP), proactively screened symptoms, and referred participants to community-based resources for identified health-related social needs. Usual care comprised nurse case management and benefits redesign (waived copayments and free transportation for any cancer care received at preferred oncology clinics in each city). The primary outcome was HRQoL. Secondary outcomes included patient activation, satisfaction with decision, ACP documentation, health care use, total health care costs, and overall survival. RESULTS A total of 160 participants were enrolled. Intervention group participants had a greater increase in mean HRQoL scores at 4-month and 12-month follow-up as compared with baseline than control group participants (expected mean difference, 11.25 [95% CI, 7.28 to 15.22]; 11.29 [95% CI, 6.96 to 15.62], respectively). CONCLUSION In this randomized trial, a CHW-led intervention significantly improved HRQoL for low-income and racial and ethnic minoritized patients with cancer more than usual care alone.
Sirtuin 2 inhibition modulates chromatin landscapes genome-wide to induce senescence in ATRX-deficient malignant glioma
Authors: Prit Benny Malgulwar, Carla Danussi, Sharvari Dharmaiah, William Johnson, Anand Singh, Kunal Rai, Arvind Rao, Jason T Huse
Journal: Neuro-Oncology (2023)

Functional inactivation of ATRX characterizes large subgroups of malignant gliomas in adults and children. ATRX deficiency in glioma induces widespread chromatin remodeling, driving transcriptional shifts and oncogenic phenotypes. Effective strategies to therapeutically target these broad epigenomic sequelae remain undeveloped.
Issues and Events
Journal: Diabetes Care (2023)

American Diabetes Association members will have the opportunity to attend monthly webinars on the second Tuesday of every month beginning in October 2023.Experts will present a variety of topics including diabetes technology, exercise physiology, behavioral medicine and psychology, and primary care.This webinar series is supported by funding from The Leona M. and Harry B. Helmsley Charitable Trust.For more information, please visit professional.diabetes.
Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression
Authors: Sandra C. Naaman, George L. Bakris
Journal: Diabetes Care (2023)

Management of diabetic kidney disease (DKD) has evolved in parallel with our growing understanding of the multiple interrelated pathophysiological mechanisms that involve hemodynamic, metabolic, and inflammatory pathways. These pathways and others play a vital role in the initiation and progression of DKD. Since its initial discovery, the blockade of the renin-angiotensin system has remained a cornerstone of DKD management, leaving a large component of residual risk to be dealt with. The advent of sodium-glucose cotransporter 2 inhibitors followed by nonsteroidal mineralocorticoid receptor antagonists and, to some extent, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has ushered in a resounding paradigm shift that supports a pillared approach in maximizing treatment to reduce outcomes. This pillared approach is like that derived from the approach to heart failure treatment. The approach mandates that all agents that have been shown in clinical trials to reduce cardiovascular outcomes and/or mortality to a greater extent than a single drug class alone should be used in combination. In this way, each drug class focuses on a specific aspect of the disease's pathophysiology. Thus, in heart failure, β-blockers, sacubitril/valsartan, a mineralocorticoid receptor antagonist, and a diuretic are used together. In this article, we review the evolution of the pillar concept of therapy as it applies to DKD and discuss how it should be used based on the outcome evidence. We also discuss the exciting possibility that GLP-1 RAs may be an additional pillar in the quest to further slow kidney disease progression in diabetes.
Doxorubicin-induced cardiovascular toxicity: a longitudinal evaluation of functional and molecular markers
Authors: Matthias Bosman, Dustin Krüger, Charles Van Assche, Hanne Boen, Cédric Neutel, Kasper Favere, Constantijn Franssen, Wim Martinet, Lynn Roth, Guido R Y De Meyer, Berta Cillero-Pastor, Leen Delrue, Ward Heggermont, Emeline M Van Craenenbroeck, Pieter-Jan Guns
Journal: Cardiovascular Research (2023)

Apart from cardiotoxicity, the chemotherapeutic doxorubicin (DOX) induces vascular toxicity, represented by arterial stiffness and endothelial dysfunction. Both parameters are of interest for cardiovascular risk stratification as they are independent predictors of future cardiovascular events in the general population. However, the time course of DOX-induced cardiovascular toxicity remains unclear. Moreover, current biomarkers for cardiovascular toxicity prove insufficient. Here, we longitudinally evaluated functional and molecular markers of DOX-induced cardiovascular toxicity in a murine model. Molecular markers were further validated in patient plasma.
Financial Toxicity Monitoring in a Randomized Controlled Trial of Patient-Reported Outcomes During Cancer Treatment (Alliance AFT-39)
Authors: Victoria S. Blinder, Allison M. Deal, Brenda Ginos, Jennifer Jansen, Amylou C. Dueck, Gina L. Mazza, Sydney Henson, Philip Carr, Lauren J. Rogak, Anna Weiss, Anna Rapperport, Mattias Jonsson, Patricia A. Spears, David Cella, Francesca Gany, Deborah Schrag, Ethan Basch
Journal: Journal of Clinical Oncology (2023)

Financial toxicity (FT) affects 20% of cancer survivors and is associated with poor clinical outcomes. No large-scale programs have been implemented to mitigate FT. We evaluated the effect of monthly FT screening as part of a larger patient-reported outcomes (PROs) digital monitoring intervention.
Ultrathin 2D Pd/Cu Single‐Atom MOF Nanozyme to Synergistically Overcome Chemoresistance for Multienzyme Catalytic Cancer Therapy
Authors: Xiaowen Guan, Xiyang Ge, Hongliang Dong, Juanjuan Wei, Jin Ouyang, Na Na
Journal: Advanced Healthcare Materials (2023)

Abstract Single‐atom nanozymes (SAzymes) have obtained increasing interest to mimic natural enzymes for efficient cancer therapy, while challenged by chemoresistance from cellular redox homeostasis and the interface of reductive species in tumor microenvironment (TME). Herein, a dual single‐atomic ultrathin 2D metal organic framework (MOF) nanosheet of multienzyme (Pd/Cu SAzyme@Dzy) is prepared to synergistically overcome chemoresistance for multienzyme enhanced cancer catalytic therapy. The Pd SAzyme exhibits peroxidase (POD)‐like catalytic activity for overcoming chemoresistance via disturbing cellular redox balance. This is further enhanced by cascade generation of more ∙OH via Cu + ‐catalyzed POD‐like reactions, initiated by in situ‐reduction of Cu 2+ into Cu + upon GSH depletion. This process can also avoid the consumption of ∙OH by endogenous reductive GSH in TME, ensuring the adequate amount of ∙OH for highly efficient therapy. Besides, the DNAzyme is also delivered for gene therapy of silencing cancer‐cell‐targeting VEGFR2 protein to further enhance the therapy. Based on both experiments and theoretical calculations, the synergetic multienzyme‐based cancer therapy is examined and the enhancement by the cascade tumor antichemoresistance is revealed.
Sustained CD28 costimulation is required for self-renewal and differentiation of TCF-1 <sup>+</sup> PD-1 <sup>+</sup> CD8 T cells
Authors: Etienne Humblin, Isabel Korpas, Jiahua Lu, Dan Filipescu, Verena van der Heide, Simon Goldstein, Abishek Vaidya, Alessandra Soares-Schanoski, Beatrice Casati, Myvizhi E. Selvan, Zeynep H. Gümüş, Andreas Wieland, Mauro Corrado, Leona Cohen-Gould, Emily Bernstein, Dirk Homann, Jerry Chipuk, Alice O. Kamphorst
Journal: Science Immunology (2023)

During persistent antigen stimulation, such as in chronic infections and cancer, CD8 T cells differentiate into a hypofunctional programmed death protein 1-positive (PD-1